Customization of deformable devices with region-selectively assembled osteoinductive microrobots via 4D bioprinting for curved joint defect repair

The in situ reconstruction of mineralized matrices within curved joint defects plays a crucial regulatory role in the functional recovery and homeostasis of surrounding soft tissues. However, achieving this with current therapeutic devices remains challenging. Inspired by the development process in natural tissues from ossification centers (OCs), a patient-specific joint repair device capable of adapting to curved joint defects and regulating the regeneration of bone mineralized matrices was developed by encoding mineralized microrobots abundant in nucleation sites via a 4D bioprinting strategy integrated with finite element analysis. The skeleton of the microrobots, prepared using a microfluidic-ice template technique, closely resembled the OCs organic matrix in both appearance and network structure. By incorporating polyphenol, the skeleton can sequentially stabilize calcium phosphate precursors via cation−π interactions to confer osteoinductive properties, bind Fe₃O₄ nanoparticles through coordination interactions, and facilitate cell loading, thereby forming locatable osteoinductive microrobots. By formulating microrobots as bioinks and pre-planning printing schemes based on differences in bioink expansion, devices with deformed shapes tailored to specific requirements and driven by an external magnetic field to calibrate their position can be customized through a finite element analysis-integrated 4D bioprinting strategy. Owing to the high water content, the devices were clearly visible in both the proton density and T2-weighted magnetic resonance imaging modes. In the printed devices, the microcomponents promoted osteogenic differentiation of cells by upregulating focal adhesion and extracellular matrix-receptor interaction signaling pathways and enriching mineralization precursors, thereby controllably regulating bone mineralized matrix generation in the heterogeneous devices. This work presents a new concept for the engineering and manufacturing of personalized curved joint defect repair devices.